Adams T E, Adams B M
Biol Reprod. 1986 Sep;35(2):360-7. doi: 10.1095/biolreprod35.2.360.
The gonadotrope cells of the ovine anterior pituitary were insulated from hypothalamic inputs by imposing an immunologic barrier generated by active immunization of ovariectomized ewes against gonadotropin-releasing hormone (GnRH) conjugated to keyhole limpet hemocyanin (KLH) through a p-aminophenylacetic acid bridge. All GnRH-KLH animals immunized developed titers of anti-GnRH that exceeded 1:5000. The antisera were specific for GnRH and cross-reacted with GnRH agonists modified in position 10 to an extent that was less than 0.01%. Ewes actively immunized against GnRH-KLH displayed levels of basal and GnRH agonist-induced gonadotropin secretion that were markedly lower (p less than 0.05) than comparable parameters in ewes actively immunized against KLH. In contrast, basal and thyrotropin-releasing hormone (TRH)-induced prolactin (PRL) secretion were not compromised by active immunization. Immunization against the GnRH-KLH conjugate, but not KLH alone, prevented expression of the positive feedback response to exogenous estradiol (E2). Pituitary stores of immunoactive luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were significantly (p less than 0.001) reduced in ewes immunized against GnRH-KLH but stores of PRL were not affected by such immunization. Further, the biopotency of the residual LH stores in tissue of animals from the anti-GnRH group was significantly (p less than 0.05) lower than LH biopotency in anti-KLH animals. Serum levels of LH in anti-GnRH ewes were restored by circhoral administration of a GnRH agonist that did not cross-react with the antisera generated. Pulsatile delivery of GnRH agonist in anti-GnRH ewes significantly (p less than 0.05) elevated serum LH within 48 h and reestablished LH levels comparable to anti-KLH ewes within 6 days of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
通过对去卵巢母羊主动免疫与钥孔戚血蓝蛋白（KLH）经对氨基苯乙酸桥偶联的促性腺激素释放激素（GnRH），建立免疫屏障，使绵羊垂体前叶的促性腺激素细胞与下丘脑输入隔离开来。所有免疫的GnRH-KLH动物产生的抗GnRH效价均超过1:5000。抗血清对GnRH具有特异性，与第10位修饰的GnRH激动剂的交叉反应率小于0.01%。主动免疫GnRH-KLH的母羊，其基础促性腺激素分泌水平和GnRH激动剂诱导的促性腺激素分泌水平，显著低于（p<0.05）主动免疫KLH的母羊的相应参数。相反，基础促甲状腺激素释放激素（TRH）诱导的催乳素（PRL）分泌不受主动免疫的影响。免疫GnRH-KLH偶联物而非单独免疫KLH，可阻止对外源性雌二醇（E2）的正反馈反应。主动免疫GnRH-KLH的母羊，垂体中免疫活性促黄体生成素（LH）和促卵泡激素（FSH）的储存显著减少（p<0.001），但PRL的储存不受此免疫的影响。此外，抗GnRH组动物组织中残余LH储存的生物活性显著低于（p<0.05）抗KLH动物中的LH生物活性。抗GnRH母羊血清中的LH水平可通过口服不与所产生抗血清发生交叉反应的GnRH激动剂恢复。在抗GnRH母羊中脉冲式给予GnRH激动剂，在48小时内显著升高（p<0.05）血清LH水平，并在治疗6天内使LH水平恢复到与抗KLH母羊相当的水平。（摘要截短至250字）
